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腺嘌呤受体 A2B 拮抗剂抑制胃癌细胞转移并增强顺铂疗效。

Adenosine Receptor A2B Antagonist Inhibits the Metastasis of Gastric Cancer Cells and Enhances the Efficacy of Cisplatin.

机构信息

159438People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region, China.

School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.

出版信息

Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338221150318. doi: 10.1177/15330338221150318.

DOI:10.1177/15330338221150318
PMID:36786018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9929921/
Abstract

Adenosine receptors play a key role in cancer progression. This study investigated the effect of the adenosine A2B receptor (ADORA2B) on epithelial-mesenchymal transition (EMT) markers and cell metastasis of gastric cancer (GC) cells. Public databases were used to investigate the specificity of ADORA2B expression in GC tissue. We used immunohistochemistry and immunofluorescence to detect ADORA2B expression in GC tissue, paracancerous tissue, and metastatic greater omental tissue. AGS and HGC-27 GC cells were selected. The effect of ADORA2B on the invasion and migration of GC cells was examined using cell scratch and transwell assays. The effect of ADORA2B on the expression of EMT marker proteins (β-catenin, N-cadherin, and vimentin) in GC cells was measured by cellular immunohistochemistry, immunofluorescence, and Western blot. The effects of an ADORA2B inhibitor combined with cisplatin on EMT markers in GC cells were further explored. The expression levels of ADORA2B in GC tissue, metastatic greater omental tissue, and lymphatic metastasis tissue were significantly higher than those in paracancerous tissue, and ADORA2B was associated with lymph node metastasis and invasion. ADORA2B significantly regulated the invasion and migration ability of GC cells and the expression levels of EMT marker proteins. The combination of an ADORA2B antagonist (PSB-603) and cisplatin had a more significant effect on reversing the expression of EMT marker proteins. ADORA2B was overexpressed in GC tissue, metastatic greater omental tissue, and metastatic lymph node tissue. ADORA2B regulated the expression of EMT marker proteins in GC cells and affected GC cell metastasis. Antagonizing ADORA2B expression increased the efficacy of cisplatin treatment.

摘要

腺苷受体在癌症进展中发挥着关键作用。本研究探讨了腺苷 A2B 受体(ADORA2B)对胃癌(GC)细胞上皮-间充质转化(EMT)标志物和细胞转移的影响。使用公共数据库研究了 ADORA2B 在 GC 组织中的表达特异性。我们使用免疫组织化学和免疫荧光法检测了 GC 组织、癌旁组织和转移性大网膜组织中 ADORA2B 的表达。选择了 AGS 和 HGC-27 GC 细胞。使用细胞划痕和 Transwell 测定法检测了 ADORA2B 对 GC 细胞侵袭和迁移的影响。通过细胞免疫组化、免疫荧光和 Western blot 测定了 ADORA2B 对 GC 细胞 EMT 标志物蛋白(β-连环蛋白、N-钙黏蛋白和波形蛋白)表达的影响。进一步探讨了 ADORA2B 抑制剂与顺铂联合对 GC 细胞 EMT 标志物的影响。GC 组织、转移性大网膜组织和淋巴结转移组织中 ADORA2B 的表达水平明显高于癌旁组织,ADORA2B 与淋巴结转移和侵袭有关。ADORA2B 显著调节 GC 细胞的侵袭和迁移能力以及 EMT 标志物蛋白的表达水平。ADORA2B 拮抗剂(PSB-603)与顺铂联合使用对逆转 EMT 标志物蛋白的表达具有更显著的效果。ADORA2B 在 GC 组织、转移性大网膜组织和转移性淋巴结组织中过度表达。ADORA2B 调节 GC 细胞中 EMT 标志物蛋白的表达,并影响 GC 细胞的转移。拮抗 ADORA2B 表达增加了顺铂治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/a8c3c13b7851/10.1177_15330338221150318-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/203d36bfe7d2/10.1177_15330338221150318-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/971cf757ccf8/10.1177_15330338221150318-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/06a5adc40783/10.1177_15330338221150318-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/049934980556/10.1177_15330338221150318-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/ed324d57fafc/10.1177_15330338221150318-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/a8c3c13b7851/10.1177_15330338221150318-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/203d36bfe7d2/10.1177_15330338221150318-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/971cf757ccf8/10.1177_15330338221150318-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/06a5adc40783/10.1177_15330338221150318-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/049934980556/10.1177_15330338221150318-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/ed324d57fafc/10.1177_15330338221150318-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/668a/9929921/a8c3c13b7851/10.1177_15330338221150318-fig6.jpg

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Metformin inhibits the development and metastasis of colorectal cancer.二甲双胍抑制结直肠癌的发展和转移。
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